Reflowed drug-polymer coated stent and method thereof

ABSTRACT

A system for forming a drug-polymer coated stent includes means for applying a polymeric coating onto at least a portion of a stent framework, means for drying the applied polymeric coating on the stent framework and means for directing a jet of heated gas towards excess coating portions of the dried polymeric coating that extend into apertures of the stent framework. The system also includes means for reflowing the polymeric coating with the directed jet of heated gas to remove the excess coating portions from the apertures of the stent framework.

RELATED APPLICATIONS

This application is a continuation of and claims the benefit of U.S.patent application Ser. No. 11/225,428 filed Sep. 12, 2005 which is adivisional application of U.S. patent application Ser. No. 10/454,652filed Jun. 4, 2003, now U.S. Pat. No. 6,979,348.

FIELD OF THE INVENTION

This invention relates generally to biomedical stents. Morespecifically, the invention relates to a drug-polymer coatedendovascular stent with a reflowed polymeric coating, and methods ofcoating thereof.

BACKGROUND OF THE INVENTION

Protective materials and bioactive drugs are used on medical devices fortreating vascular conditions such as stents. With generally opencylindrical scaffolding, stents typically have apertured or lattice-likewalls of a metallic or polymeric base, and can be either balloonexpandable or self-expanding. A stent is typically deployed by mountingthe stent on a balloon portion of a balloon catheter, positioning thestent in a body lumen, and expanding the stent by inflating the balloon.The balloon is then deflated and removed, leaving the stent in place.Stents help reduce the probability and degree of vessel blockage fromrestenosis.

Various approaches for providing localized drug delivery using coatedstents have been under investigation and marketed for some time. Avariety of stent coatings and compositions have been proposed to providelocalized therapeutic pharmacological agents and treatment of a vesselat the site being supported by the stent. Stent coatings with variousfamilies of drug polymer chemistries have been used to increase theeffectiveness of stenting procedures and to control drug-elutionproperties. For example, polymeric coatings can be made frompolyurethane, polyester, polylactic acid, polyamino acid,polyorthoester, or polyphosphate ester. Examples of drug or bioactiveagents include antirestonotic and anti-inflammatory compounds.

Medical research indicates a greater effectiveness of vascular stentswhen the stents are coated with pharmaceutical drugs that help preventor treat medical conditions such as restenosis and thrombosis. Thesedrugs may be released from a coating while in the body, delivering theirpatent effects at the site where they are most needed. The localizedlevels of the medications can be elevated, and therefore potentiallymore effective than orally or intravenously delivered drugs.Furthermore, drugs released from tailored stent coatings can havecontrolled, timed-release qualities, eluting their bioactive agents overhours, weeks or even months. Stent coatings typically have a drug oractive agent, which has been dissolved or dispersed throughout thepolymeric material and physically constrained within the polymer. Thesustained release of drugs generally relies upon either controlleddegradation of the polymer or diffusion through the polymer to controlthe elution of the compounds.

Stents can be coated with a polymer or combination of a polymer and apharmaceutical agent or drug by application techniques such as dipping,spraying, painting, and brushing. Typical methods of coating, such asspraying, dipping and brushing techniques, can be susceptible to adegree of pooling, bridging, or webbing on stent structures and struts,problems recognized by those skilled in the art of manufacturing stents.

Several solutions have been suggested. One solution in a manual dippingprocess blows excessive material off an open stent framework, asdisclosed in “Coating” by Taylor et al., U.S. Pat. No. 6,214,115 issuedApr. 10, 2001. The process addresses the problems of inconsistent dryingand blockage of openings. Hossainy and others disclose another dippingprocess that addresses the issues of blockage and bridging between stentstruts in “Process for Coating Stents”, U.S. Pat. No. 6,153,252 issuedNov. 28, 2000. Flow or movement of the coating fluid through theopenings in the perforated medical device is used to avoid the formationof blockages or bridges. The flow system may use a perforated manifoldinserted in the stent to circulate the coating fluid, or may place thestent on a mandrel or in a small tube that is moved relative to thestent during the coating process.

Another coating method that uses airflow is disclosed in “CoatingMedical Devices Using Air Suspension”, Schwarz et al., InternationalPatent Application WO 00/62830 published Oct. 26, 2000. The proposedmethod suspends a medical device in air and introduces a coatingmaterial into an air stream such that the material is dispersed thereinto coat at least a portion of the device.

In addition to controlling any excessive coating material, an effectivecoating method needs to result in a lubricious or smooth outer surfaceof the coated stent, thereby reducing the probability of abrasions tobody tissue as a stent is deployed. One coating method that optionallyapplies a solvent by dipping or spraying on an already coated stent tosmooth the outer surface of the coating is described by Ding in “Methodof Applying Drug-Release Coatings”, U.S. Pat. No. 5,980,972 issued Nov.9,1999. The method uses two solutions: one with a polymer dissolved in afirst solvent and another with a drug dissolved or suspended in a secondsolvent. When a third solvent is used to smooth the stent coating, thesolvent needs to be compatible with the polymer matrix.

In another example, a collagen liner material forms a lubricious surfaceover the stent to protect the vascular wall and form a non-thrombogeniccushion for the stent in the vascular lumen, as disclosed in “Stent withCollagen”, Buirge et al., U.S. Pat. No. 5,693,085 issued Dec. 2, 1997.

Another smooth stent surface is described in “Stent Lining”, Sahatjianet al., U.S. Pat. No 6,364,893, issued Apr. 2, 2002. A stent is linedwith a hydrogel to reduce shear forces and flow disturbances in theblood, to protect damaged cells adjacent to the stent, to reduceplatelet deposition at the stent site, and to deliver a drug to reduceor prevent restenosis of stent lumens. The expandable stent is mountedon a catheter balloon, which is coated with a hydrogel. The stent isdelivered in a contracted condition to a targeted site in a body wherethe expanding balloon lodges the stent in the body with the hydrogelcoated on the inner surfaces of the stent as a lining.

Drug polymer coatings on medical devices need to adhere well to thesubstrate or surface of the medical device and be mechanically pliant,because the devices often undergo significant flexion or expansionduring the delivery and deployment. Excess coating material that canoccur between struts of the stent needs to be removed or controlled toprevent cracking or flaking during or after the deployment of the stent.A stent deployed by self expansion or balloon expansion is accompaniedby a high level of bending at portions of the stent framework, which cancause cracking, flaking, peeling, or delaminating of many candidate drugpolymers when the stent diameter is increased by threefold or moreduring expansion. In addition, any step within the process for coating apre-deployed stent should not cause a drug-polymer to fall off,crystallize or melt.

Accordingly, a desirable, efficient and improved coating method wouldprovide a well-adhered coating with a smooth outer surface of a medicaldevice. In addition, the method would minimize or eliminate the pooling,bridging, or webbing of excess coating material between structures suchas stent struts. In addition, the stent associated with this method hasa smoother coating topography with one or more well adhered drug-polymercoatings that maintain mechanical integrity during stent deployment andprovide a desired elution rate for one or more drugs, overcoming thedeficiencies and limitations described above.

SUMMARY OF THE INVENTION

One aspect of the invention provides a system for forming a drug-polymercoated stent. The system includes means for applying a polymeric coatingonto at least a portion of a stent framework, means for drying theapplied polymeric coating on the stent framework and means for directinga jet of heated gas towards excess coating portions of the driedpolymeric coating that extend into apertures of the stent framework. Thesystem also includes means for reflowing the polymeric coating with thedirected jet of heated gas to remove the excess coating portions fromthe apertures of the stent framework

Another aspect of the invention provides a system for forming adrug-polymer coated stent that includes a dipping tank, a polymericsolution contained within the dipping tank and a transport mechanismoperably connected to a stent framework holding device. The system alsoincludes at least one stent framework releasably connected to thetransport mechanism and a gas supply system for directing a heated andpressurized gas towards excess coating contained within apertures of thecoated stent.

The present invention is illustrated by the accompanying drawings ofvarious embodiments and the detailed description given below. Thedrawings should not be taken to limit the invention to the specificembodiments, but are for explanation and understanding. The detaileddescription and drawings are merely illustrative of the invention ratherthan limiting, the scope of the invention being defined by the appendedclaims and equivalents thereof. The foregoing aspects and otherattendant advantages of the present invention will become more readilyappreciated by the detailed description taken in conjunction with theaccompanying drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

Various embodiments of the present invention are illustrated by theaccompanying figures, wherein:

FIG. 1 is an illustration of a system for treating a vascular conditionincluding a drug-polymer coated stent coupled to a catheter, inaccordance with one embodiment of the current invention;

FIG. 2 is a cross-sectional view of a drug-polymer coated stent, inaccordance with one embodiment of the current invention;

FIG. 3 is an illustration of a system for forming a drug-polymer coatedstent, in accordance with one embodiment of the current invention; and

FIG. 4 is a flow diagram of a method of forming a drug-polymer coatedstent, in accordance with one embodiment of the current invention.

DETAILED DESCRIPTION OF THE PRESENTLY PREFERRED EMBODIMENTS

FIG. 1 illustrates a system for treating a vascular condition,comprising a drug-polymer coated stent coupled to a catheter, inaccordance with one embodiment of the present invention at 100. Vascularcondition treatment system 100 includes a drug-polymer coated stent 120coupled to a delivery catheter 110. Coated stent 120 includes a stentframework 130 and a reflowed drug-polymer coating 140 disposed on atleast a portion of stent framework 130. Generally tubular in shape withopen ends, the latticework of stent framework 130 has a plurality ofopen apertures 132 between the struts, shaped to allow expansion ofstent framework 130 from an initially contracted form when deployed.

Drug-polymer coating 140 includes a polymeric coating 142 positionedadjacent to stent framework 130 and at least one therapeutic agent 144encased by or interdispersed within drug-polymer coating 140. In somecases, drug-polymer coating 140 includes a cap coating 148 disposed onreflowed drug-polymer coating 140. Drug-polymer coating 140 can providetime-released delivery of one or more therapeutic agents to surroundingtissue after coated stent 120 has been deployed within a vessel of thebody.

Insertion of coated stent 120 into a vessel in the body helps treat, forexample, heart disease, various cardiovascular ailments, and othervascular conditions. Catheter deployed coated stent 120 typically isused to treat one or more blockages, occlusions, stenoses, or diseasedregions in the coronary artery, femoral artery, peripheral arteries, andother arteries in the body. Treatment of vascular conditions involvesthe prevention or correction of various ailments and deficienciesassociated with the cardiovascular system, the cerebrovascular system,urinogenital systems, biliary conduits, abdominal passageways and otherbiological vessels within the body.

An exemplary drug-polymer coating 140 includes or encapsulates one ormore therapeutic agents. Drug-polymer coating 140 may comprise one ormore therapeutic agents 144 dispersed within or encased by drug-polymercoating 140 on coated stent 120, which are eluted from coated stent 120with controlled time delivery after deployment of coated stent 120 inthe body. A therapeutic agent is capable of producing a beneficialeffect against one or more conditions including coronary restenosis,cardiovascular restenosis, angiographic restenosis, arteriosclerosis,hyperplasia, and other diseases or conditions. For example, thetherapeutic agent can be selected to inhibit or prevent vascularrestenosis, a condition corresponding to a narrowing or constricting ofthe diameter of the bodily lumen where the stent is placed. Drug-polymercoating 140 may comprise, for example, an antirestenotic drug such asrapamycin, a rapamycin analogue, or a rapamycin derivative to prevent orreduce the recurrence or narrowing and blockage of the bodily vessel.Drug-polymer coating 140 may comprise an anti-cancer drug such ascamptothecin or other topoisomerase inhibitors, an antisense agent, anantineoplastic agent, an antiproliferative agent, an antithrombogenicagent, an anticoagulant, an antiplatelet agent, an antibiotic, ananti-inflammatory agent, a steroid, a gene therapy agent, an organicdrug, a pharmaceutical compound, a recombinant DNA product, arecombinant RNA product, a collagen, a collagenic derivative, a protein,a protein analog, a saccharide, a saccharide derivative, a bioactiveagent, a pharmaceutical drug, a therapeutic substance, or a combinationthereof.

The elution rates of the therapeutic agents and total drug eluted intothe body and the tissue bed surrounding the stent framework are based onthe thickness of drug-polymer coating 140; the constituency ofdrug-polymer coating 140; the nature, distribution and concentration ofthe therapeutic agents; the thickness and composition of any cap coat,and other factors. Drug-polymer coating 140 may include and elutemultiple therapeutic agents to achieve the desired therapeutic effect.Drug-polymer coating 140 can be tailored to control the elution of oneor more therapeutic agents that are transported through the coatingprimarily by diffusion processes. In some cases, a portion of thepolymeric coating is absorbed into the body, releasing therapeuticagents embedded within or encased by the coating. In other cases,drug-polymer coating 140 erodes from coated stent 120 to release thetherapeutic agents, the residual polymer being expelled by the body. Capcoating 148 can be selected to provide a diffusion barrier to thetherapeutic agents and aid in the control of drug elution.

Incorporation of a drug or other therapeutic agents into drug-polymercoating 140 allows, for example, the rapid delivery of apharmacologically active drug or bioactive agent within twenty fourhours following the deployment of a stent, with a slower, steadydelivery of a second bioactive agent over the next three to six months.For example, the therapeutic agent may comprise an antirestenotic drugsuch as rapamycin, a rapamycin analogue, or a rapamycin derivative. Asecond therapeutic agent may comprise, for example, an anti-inflammatantsuch as dexamethasone. The therapeutic agent constituency in thedrug-polymer coating may be, for example, between 0.1 percent and 50percent of the drug-polymer coating by weight.

Catheter 110 of an exemplary embodiment of the present inventionincludes a balloon 112 that expands and deploys the stent within avessel of the body. After positioning coated stent 120 within the vesselwith the assistance of a guide wire traversing through a guidewire lumen114 inside catheter 110, balloon 112 is inflated by pressurizing a fluidsuch as a contrast fluid that fills a tube inside catheter 110 andballoon 112. Coated stent 120 is expanded until a desired diameter isreached, and then the contrast fluid is depressurized or pumped out,separating balloon 112 from coated stent 120 and leaving coated stent120 deployed in the vessel. Alternatively, catheter 110 may include asheath that retracts, allowing the expansion of a self-expanding versionof coated stent 120.

FIG. 2 shows a cross-sectional view of a drug-polymer coated stent, inaccordance with one embodiment of the present invention at 200. Adrug-polymer coated stent 220 includes a stent framework 230 with adrug-polymer coating 240 disposed on stent framework 230. Drug-polymercoating 240 includes a polymeric coating 242 positioned adjacent tostent framework 230 and a therapeutic agent 244 encased by orinterdispersed within polymeric coating 242.

Drug-polymer coating 240 typically encases stent framework 230, forminga relatively thin coating around the struts and latticework of stentframework 230. During processing, one or more excess coating portions246 may occur in apertures 232 of stent framework 230 between the strutsand open areas of the latticework. During coating operations such asdipping, spraying, brushing or painting, polymeric solution may pool,web, or bridge in apertures 232, resulting in one or more excess coatingportions 246, particularly near places where stent framework 230 isheld. Excess coating portions 246 can be removed from apertures 232 ofstent framework 230 by heating and reflowing polymeric coating 242,resulting in a reflowed drug-polymer coating 240 a around stentframework 230 a proximate to apertures 232 in stent framework 230 withexcess portions 246 removed from apertures 232. Reflowing drug-polymercoating 240 or polymeric coatings 242 may also result in improvedsurface smoothness of the coating and enhanced adhesion to the metallicor polymeric base of stent framework 230 or to any underlying coatings.

Stent framework 230 comprises a metallic base or a polymeric base, suchas stainless steel, nitinol, tantalum, MP35N alloy, platinum, titanium,a chromium-based alloy, a cobalt-based alloy, a suitable biocompatiblealloy, a suitable biocompatible material, a biocompatible polymer, or acombination thereof. The polymeric base material may comprise anysuitable polymer for biomedical stent applications, as is known in theart.

Drug-polymer coating 240 includes a polymeric coating 242 with a polymersuch as poly(vinyl alcohol) (PVA), poly(ethylene-vinyl acetate) (PEVA),polyurethane (PU), polycaprolactone (PCL), polyglycolide (PGA),poly(lactide-co-glycolide) (PLGA), poly(ethylene oxide) (PEO),poly(vinyl pyrrolidone) (PVP), silicone, an acrylic polymer, an acrylicand acrylonitrile copolymer, a latex polymer, a thermoplastic polymer, athermoset polymer, a biostable polymer, a biodegradable polymer, ablended polymer, a copolymer, or a combination thereof. The polymer maybe applied using a technique such as dipping or spraying with limiteddrying or limited crosslinking to achieve the desired level oftackiness.

Drug-polymer coating 240 comprises at least one therapeutic agent 244.Therapeutic agent 244 may be mixed with polymeric coating 242 prior tothe application of drug-polymer coating 240, or added to polymericcoating 242 after the application of polymeric coating 242 onto stentframework 230. Therapeutic agent 244 may be in any suitable form such asa liquid, a gel, a powder, a particle, a granulated drug, a micronizeddrug, a pelletized drug, a microencapsulated drug, a nanoencapsulateddrug, or a combination thereof.

Although illustrated with one layer of drug-polymer coating 240,multiple coatings of the polymer or drug-polymer may be disposed onstent framework 230 to provide a thicker composite coating and a largerquantity of therapeutic agents. Multiple therapeutic agents may bearranged within drug-polymer coating 240 to provide a controltime-delivery of each therapeutic agent. For example, tailoring thethickness and constituency of each drug-polymer coating 240, thedistribution and concentration of the therapeutic agents, and inclusionof an optional cap coating helps control the elution rate of one or moretherapeutic agents dispersed within or encased by drug-polymer coating240. Drug elution refers to the transfer of a therapeutic agent fromdrug-polymer coating 240 to the surrounding area in a body. The amountof drug eluted is determined as the total amount of therapeutic agentexcreted out of drug-polymer coating 240, typically measured in units ofweight such as micrograms, or in weight per peripheral area of thestent. The concentration of the therapeutic agent included withdrug-polymer coating 240 is between, for example, 0.1 percent and 50percent by weight.

FIG. 3 shows an illustration of a system for forming a drug-polymercoated stent, in accordance with one embodiment of the current inventionat 300. Drug-polymer coating system 300 includes a polymeric solution350 in a dipping tank 352 and a transport mechanism 322 such as a clampor a tether for holding and transporting stents in and out of tank 352either manually or automatically. Multiple stent frameworks 330 arereadily accommodated for dipping and drying in a batch or continuousbatch process. A mandrel 360 with cones 362 at each end of stentframework 330 may be used, for example, to hold stent framework 330during dipping and reflowing.

In one example, polymeric solution 350 includes at least one polymer354, a therapeutic agent 356, and a solvent 358. Stent framework 330 isdipped into polymeric solution 350 and dried, for example, bypositioning the dipped stent framework 330 in air and evaporating muchor all of solvent 358 to form a drug-polymer coating 340 on stentframework 330. The components of polymeric solution 350 and the dippingtreatments are selected to provide a drug-polymer coating 340 on stentframework 330 with the desired thickness and quantity of therapeuticagents. In one example, polymeric solution 350 includes a polymer 354such as poly(vinyl alcohol), poly(ethylene-vinyl acetate), polyurethane,polycaprolactone, polyglycolide, poly(lactide-co-glycolide),poly(ethylene oxide), poly(vinyl pyrrolidone), silicone, an acrylicpolymer, an acrylic and acrylonitrile copolymer, a latex polymer, athermoplastic polymer, a thermoset polymer, a biostable polymer, abiodegradable polymer, a blended polymer, a copolymer, or a combinationthereof, along with a suitable solvent 358 that is compatible withpolymer 354 and the therapeutic agents 356. In another example,drug-polymer coating 340 is applied onto stent framework 330 by sprayingor brushing. Stent framework 330 is generally dipped into polymericsolution 350 for a prescribed period of time, and removed for drying inair or in an oven. Additional dipping or spraying steps may be used toachieve a thicker drug-polymer coating 340.

Drug-polymer coating 340 can be baked in an oven at an elevatedtemperature to further drive off buried pockets of solvent and toprovide a desired level of crosslinking of the polymers.

After applying polymeric coating 342 onto at least a portion of stentframework 330 and drying applied polymeric coating 342, coated stent 320may have excess coating portions 346 extending from the struts andlatticework into apertures 332 of stent framework 330. In the detailedview, drug-polymer coating 340 has excess coating portions 346 with oneor more webbed regions, pooled regions, bridged regions, or combinationsthereof extending into apertures 332 a of stent framework 330 a. Coatedstent 320 with excess coating portions 346 may be positioned in front ofa jet of heated gas 370 emitted from a gas nozzle 372. Apertures 332 ofstent framework 330 with excess coating portions 346 may be positionedadjacent to jet of heated gas 370. Dried polymeric coating 342 may beheated above a reflow temperature of dried polymeric coating 342. Driedpolymeric coating 342 is reflowed with the directed jet of heated gas370 to remove excess coating portions 346 from apertures 332 of stentframework 330.

The heated gas 370 ejected from gas nozzle 372 may be supplied, forexample, from a pressurized gas tank 374 and heated in a heater 376. Theheated gas 370 may be adjusted and controlled with a gas valve 378 by amicroprocessor-controlled controller 380. Controller 380 may beautomatic or semi-automatic, receiving commands and settings from a useror a control computer to appropriately position coated stent 320,pressurizing and heating gas 370, and adjusting the ejection temperatureand the ejection velocity of the ejected gas 370. In a fully automaticsystem, positioning and inspection capability can be added for real-timecontrol and inspection to determine excess coating portions 346 andremove them. In one example of a manual system, the temperature of theheated gas is controlled and the gas velocity is manually controlled. Afilter may be included to remove particles from gas 370.

After the reflow of polymeric coating 342 has been completed and thecoated stent 320 has cooled, excess coating portions 346 have beenremoved and apertures 332 b of stent framework 330 b are clear of anyexcess coating portions 346, leaving drug-polymer coating 340 on thestruts and latticework of stent framework 330 b, as shown in thedetailed view of stent framework 330 b.

Multiple dipping, drying and reflow steps can be used to applyadditional drug-polymer coatings 340 or other polymeric coatings 342onto stent framework 330. The reflow steps can be used to clearbridging, pooling and webbing of excess polymer and drug polymer afterone or more applications of a primer coating, a drug-polymer coating, acap coating, or a combination thereof.

FIG. 4 shows a flow diagram of a forming a drug-polymer coated stent, inaccordance with one embodiment of the present invention at 400.Drug-polymer application method 400 includes various steps to form andreflow a drug-polymer coating on a stent framework with an optionalprimer coating or an optional cap coating.

A stent framework is provided and cleaned, as seen at block 405. Thestent framework may be cleaned, for example, by inserting the stentframework into various solvents, degreasers and cleansers to remove anydebris, residues, or unwanted materials from the surface of the stentframework. The stent framework is dried, and generally inspected at thispoint in the process. Generally, a primer coating is not required,though a primer coating may be applied to the stent framework prior toapplication of the polymer or drug-polymer coating. The primer coatingis dried to eliminate or remove any volatile components and then curedor crosslinked as needed. Excess liquid may be blown off prior to dryingthe primer coating, which may be done at room temperature or at elevatedtemperatures under dry nitrogen or other suitable environments includinga vacuum environment.

A polymeric coating is applied onto at least a portion of the stentframework, as seen at block 410. The polymeric coating may comprise, forexample, a primer coating, a drug-polymer coating, a cap coating, or acombination thereof. The polymeric coating is applied using any suitablecoating technique such as dipping, spraying, painting, or brushing.Exemplary applied polymeric coatings comprise polymers such aspoly(vinyl alcohol), poly(ethylene-vinyl acetate), polyurethane,polycaprolactone, polyglycolide, poly(lactide-co-glycolide),poly(ethylene oxide), poly(vinyl pyrrolidone), silicone, an acrylicpolymer, an acrylic and acrylonitrile copolymer, a latex polymer, athermoplastic polymer, a thermoset polymer, a biostable polymer, abiodegradable polymer, a blended polymer, a copolymer, and combinationsthereof. In one embodiment of the present invention, one or moretherapeutic agents may be added to and dispersed within the polymericcoating before its application onto the stent framework.

The dipped, sprayed or brushed stent framework is then dried, as seen atblock 415. The coated stent framework may be dried, for example, bypositioning the coated stent framework in air and evaporating anysolvent from the applied polymeric coating. The polymeric coating isgenerally dried after application by evaporating off the solvent at roomtemperature and under ambient conditions. A nitrogen environment orother controlled environment may also be used for drying. Alternatively,the polymeric coating can be dried by evaporating the majority of anysolvent at room temperature, and then further drying the coating in avacuum environment between, for example, a room temperature of about 25degrees centigrade and 50 degrees centigrade or higher. Drying in avacuum environment helps to extract any pockets of solvent buried withinthe polymeric coating and to provide the desired level of crosslinkingin the polymer. After application and drying of the polymeric coating,excess coating portions may extend into apertures of the stent frameworkby webbing, pooling or bridging of the polymeric coating between strutsand latticework of the stent framework.

The apertures of the stent framework that have excess coating portionsmay be positioned adjacent to a jet of heated gas, as seen at block 420.The coated stent framework may be positioned manually or automaticallysuch that a portion of the stent framework with the excess coatingportions is placed in front of jet of heated gas. The heated gas may beemitted from, for example, one or more gas nozzles, one or more holes ina manifold positioned near the coated stent framework, or from a seriesof holes in a mandrel that is holding the coated stent framework withcups or cones at each end.

One or more jets of heated gas are directed towards excess coatingportions of the dried polymeric coating, as seen at block 425. Theexcess coating portions extend into apertures of the stent framework.The heated gas is directed onto the excess coating portions, softeningand sometimes melting the polymeric material. For example, the directedjet of heated gas may be pressurized and ejected from a gas nozzle orfrom holes in a tube or manifold. In some cases, the jets of heated gasare directed or scanned along the entire coated stent framework; inother cases, the heated gas is emitted from one or more gas nozzles anddirected at only the excess coating portions. The directed jet of heatedgas may comprise, for example, a gas such as nitrogen, argon, or air. Afilter may be used to remove large particles from the jets of heatedgas.

The temperature and velocity of the heated gas may be adjusted, forexample, to effectively remove excess coating portions from theapertures and to reflow the polymeric coating onto the stent framework.The temperature of the directed jet of heated gas may have an ejectiontemperature, for example, between 25 degrees centigrade and 500 degreescentigrade, although a typical ejection temperature is between 100degrees centigrade and 150 degrees centigrade. The type of polymer anddrug used in the formulation may impose limits on the temperature of theheated gas. The velocity of the directed jet of heated gas may have anejection velocity, for example, of greater than two meters per second.

The dried polymeric coating may be heated close to or above a reflowtemperature of the dried polymeric coating, as seen at block 430. Forexample, a polymeric coating with a glass transition temperature of 150degrees centigrade may be heated to a reflow temperature of 140 degreeswhere the polymeric coating is soft and can reflow. In another example,the excess coating portions are locally heated to a reflow temperatureabove the glass transition temperature, so that the excess polymericcoating liquefies and is blown away or reflows onto the coated stentframework where it cools and hardens. In another example, the coatedstent framework is pre-heated prior to directing heated gas into theapertures and reflowing the excess coating portions.

The polymeric coating is reflowed to remove excess coating portions, asseen at block 435. The polymeric coating may be reflowed by heating thepolymeric coating with directed jets of heated gas for a sufficientperiod of time so that excess coating portions from the apertures of thestent framework are removed. Excess coating portions may be caused, forexample, by webbing, pooling or bridging between struts and open spacesin the latticework of the stent framework. Excess coating portions mayoccur near the ends of the stent framework where the stent framework isheld with cones or cups to a mandrel, or at frayed regions where theholding apparatus has been removed. The reflowed polymeric coating maybe blown off the stent framework, although the polymeric coating isusually heated to melt and fuse the excess coating portions proximate tothe apertures in the stent framework. When heated, the polymeric coatinggenerally reflows and reshapes around the struts and latticework of thestent framework. Reflowing the polymeric coatings and drug-polymercoatings, in addition to alleviating bridging, pooling and webbing, mayalso improve surface smoothness of the coatings and enhance adhesion tothe stent framework or any underlying coatings. After the removal of theheated gas, the polymeric coating and the stent framework is cooled.

The coated stent framework with the reflowed polymeric coating may bere-positioned, as seen back at block 420, to remove excess coatingportions from any remaining untreated apertures, until all excesscoating portions have been removed from the apertures.

The polymeric coating may be reflowed and excess coating portionsremoved at the end of each application and drying step, such as after anapplication of a primer coating, after an application of eachdrug-polymer coating, and after an application of a cap coating.Additional coatings may be applied to the coated stent framework, asseen back at block 410. Subsequent coatings may be applied, for example,by repeated dipping into the same polymeric solution in a dipping tank.Other coatings may be applied, for example, by dipping the coated stentframework into a separate tank with another polymeric solutioncomprising a different polymer or a different therapeutic agent. Thethickness, constituency and concentrations of the various layers can beapplied and controlled to achieve the desired coating structure.

For example, a cap coating may be applied onto the polymer-coated stentframework. The cap coating is applied by using, for example, anysuitable application technique such as dipping, spraying, brushing orpainting. The cap coating provides a level of scratch and abrasionresistance during the handling of the coated stent, and can serve as adiffusion barrier that provides additional control over the elution oftherapeutic agents from the drug-polymer coating after deployment of thestent within the body. The cap coating may be formed from polymers suchas polycaprolactone, polyglycolide, poly(lactide-co-glycolide), asilicone-urethane copolymer, a polyurethane, or poly(ethylene-vinylacetate). Multiple cap coats may be applied to achieve a thicker capcoating.

The reflow process allows for a higher concentration of solids in thepolymeric solution during dipping or spraying, requiring less solventand providing for a thicker coating on the stent framework withoutbridging, pooling or webbing.

The reflowed polymeric coating may be baked after removing the excesscoating portions from the apertures of the stent framework, as seen atblock 440. The reflowed polymeric coating may be baked in an oven underan inert environment such as nitrogen or vacuum, removing any remainingsolvent and providing for further crosslinking of the polymeric coating.For example, the coated stent framework with the reflowed polymericcoating may be dried in a vacuum oven at 45 degrees centigrade fortwenty minutes or more.

Other variations such as the application and reflowing of a drug-polymercoating prior to application of a cap coating are possible and withinthe spirit and scope of the present invention.

The coated stent may be crosslinked and sterilized as needed, as seen atblock 445. Crosslinking may be done by providing additional dryingcycles in air, or by heating the coated stent above a curing temperaturein an oven with a controlled ambient such as vacuum, nitrogen, or air.Sterilization may employ, for example, gamma-ray irradiation, e-beamradiation, ethylene oxide gas, or hydrogen peroxide gas plasmasterilization techniques. The coated stent may be packaged, shipped, andstored in a suitable package until it is used.

A delivery catheter may be coupled to the coated stent, as seen at block450. The delivery catheter may include an inflatable balloon that ispositioned between the coated stent and the catheter and used fordeploying the coated stent in the body. Alternatively, the deliverycatheter may include a sheath that retracts to deploy a self-expandingversion of the coated stent.

In one exemplary method, fully processed coated stents are reduced indiameter and placed into the distal end of the catheter to form aninterference fit, which secures the stent onto the catheter. Thecatheter with the stent may be placed in a catheter package andsterilized prior to shipping and storing. Before clinical use, the stentis sterilized by any appropriate or medically conventional means.

When ready for deployment, the drug-polymer coated stent is insertedinto a vessel of the body. The drug-polymer coated stent is insertedtypically in a controlled environment such as a catheter lab orhospital. The delivery catheter, which helps position the drug-polymercoated stent in a vessel of the body, is typically inserted through asmall incision of the leg and into the femoral artery, and directedthrough the vascular system to a desired place in the vessel. Guidewires threaded through an inner lumen of the delivery catheter assist inpositioning and orienting the drug-polymer coated stent. The position ofthe drug-polymer coated stent may be monitored, for example, with afluoroscopic imaging system or an x-ray viewing system in conjunctionwith radiopaque markers on the coated stent, radiopaque markers on thedelivery catheter, or contrast fluid injected into an inner lumen of thedelivery catheter and into an inflatable catheter balloon that iscoupled to the drug-polymer coated stent. The stent is deployed, forexample, by expanding the stent with a balloon or by extracting a sheaththat allows a self-expandable stent to enlarge after positioning thestent at a desired location within the body.

Once the coated stent is deployed, the therapeutic agents in thedrug-polymer coating are eluted. The elution rates of the therapeuticagents into the body and the tissue bed surrounding the stent frameworkare based on the polymers, thickness of the drug-polymer coating and anycap coating, and the distribution and concentration of the therapeuticagents contained therein, among other factors.

While the embodiments of the invention disclosed herein are presentlyconsidered to be preferred, various changes and modifications can bemade without departing from the spirit and scope of the invention. Thescope of the invention is indicated in the appended claims, and allchanges that come within the meaning and range of equivalents areintended to be embraced therein.

1. A system for forming a drug-polymer coated stent, comprising: meansfor applying a polymeric coating onto at least a portion of a stentframework; means for drying the applied polymeric coating on the stentframework; means for directing a jet of heated gas towards excesscoating portions of the dried polymeric coating, the excess coatingportions extending into apertures of the stent framework; and means forreflowing the polymeric coating with the directed jet of heated gas toremove the excess coating portions from the apertures of the stentframework.
 2. The system of claim 1 wherein the means for applying thepolymeric coating onto the stent framework comprises one of dipping,spraying, or brushing the stent framework with a polymeric solution. 3.The system of claim 1 wherein the applied polymeric coating comprises atleast one of a primer coating, a drug-polymer coating, or a cap coating.4. The system of claim 1 wherein the directed jet of heated gas ispressurized and ejected from a gas nozzle.
 5. The system of claim 1wherein the directed jet of heated gas has an ejection temperaturebetween 25 degrees centigrade and 500 degrees centigrade.
 6. The systemof claim 1 wherein the directed jet of heated gas has an ejectionvelocity greater than two meters per second.
 7. The system of claim 1further comprising: means for positioning the apertures of the stentframework with the excess coating portions adjacent to the jet of heatedgas.
 8. The system of claim 1 further comprising: means for heating thedried polymeric coating above a reflow temperature of the driedpolymeric coating.
 9. The system of claim 1 further comprising: meansfor adjusting an ejection velocity and an ejection temperature of thedirected jet of heated gas.
 10. The system of claim 1 furthercomprising: means for baking the reflowed polymeric coating afterremoving the excess coating portions from the apertures of the stentframework.
 11. A system for forming a drug-polymer coated stent,comprising: a dipping tank; a polymeric solution contained within thedipping tank; a transport mechanism operably connected to a stentframework holding device; at least one stent framework releasablyconnected to the stent framework holding device; and a gas supplysystem, the gas supply system comprising: a controller, a pressurizedgas tank operably connected to the controller, a heater operablyconnected to the gas tank for heating the pressurized gas, a gas nozzlefor directing the heated pressurized gas; and a gas valve positionedbetween the heater and gas nozzle for adjusting and controlling the flowof pressurized gas from the heater.
 12. The system of claim 11 whereinthe transport mechanism comprises a clamp or tether.
 13. The system ofclaim 11 wherein the stent framework holding device comprises a mandrel.14. The system of claim 13 wherein the mandrel includes a first cone anda second cone, and wherein the stent framework is positioned between thefirst cone and the second cone.
 15. The system of claim 11 wherein thepolymeric solution comprises at least one polymer, at least onetherapeutic agent and a solvent.